Tyche Industries Ltd — February 06, 2025

Failure to record all quality-related activities at the time they are performed.

Your quality unit (QU) failed to ensure the integrity of CGMP records. For example, during the inspection, a member of your management stated that two of your operators admitted to falsifying temperature data for a drying oven that was not turned on during the manufacture of a (b)(4) batch, which later failed to meet the residual solvents specification. In addition, an Assistant Manager in Production, an Assistant Manager in Quality Assurance, and a Quality Control Manager admitted to participating in the preparation of a “backdated calculation sheet” that was given to our investigator.

Your documentation practices were not indicative of a facility that is in compliance with CGMP.

2. Failure to clean equipment and utensils to prevent contamination or carry-over of a material that would alter the quality of the APIs beyond the official or other established specifications.

FDA documented rust-like residues inside (b)(4) non-dedicated (b)(4) used in the production of (b)(4). In addition, FDA documented bare footprints inside another (b)(4) used in the production of (b)(4). Each (b)(4) was labeled that it had been cleaned and was ready for use.

Inadequately cleaned and maintained manufacturing equipment can lead to potential cross- contamination that could compromise your API’s quality and safety.

Your response is inadequate. You state that you reviewed the quality of the products manufactured in the impacted equipment since February 2024, but you do not describe how you conducted this review, nor the reason you limited your review to this timeframe. In addition, you do not adequately explain how you will prevent the failure to clean equipment after personnel enter inside it from recurring. Finally, you state that personnel entering inside equipment should “wear cloth shoe cover after removing shoe,” but failing to wear suitable clothing, including appropriate footwear, poses an unacceptable risk to the product.

In your response to this letter, provide:

Your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review.

3. Failure to test the identity of each batch of incoming production material.

Your incoming raw material used to manufacture API intended for the U.S. market was not adequately tested. For example, you did not test the (b)(4) used as a raw material in the production of (b)(4) for identity.

Your response is inadequate. You state that you “initiated the activity” to test (b)(4) for identity. However, you do not address whether all other raw materials are tested for identity or how you will prevent this deviation from recurring with new raw materials.

In your response to this letter, provide:

A comprehensive, independent review of your material system to determine whether all suppliers of raw materials, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable raw materials, containers, and closures.
The chemical and microbiological quality control specifications you use to test and release each incoming batch of raw material for use in manufacturing.
A description of how you will test each raw material batch for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s certificates of analysis (COAs) instead of testing each raw material batch for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming raw material batch.
A summary of results obtained from testing all raw materials to evaluate the reliability of the COA from each raw material manufacturer. Include your standard operating procedure that describes this COA validation program.
A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.
Data Integrity Remediation



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